Volume 4,Issue 5
龙血素A 对JAK2/STAT3信号通路减轻MIRI的机制研究
心血管疾病已成为严重威胁人类健康的重大公共卫生问题，心肌梗死致死率居高不下。临床血运重建虽能挽救缺血心肌，但可引发心肌缺血再灌注损伤（MIRI），其机制与活性氧大量生成、细胞凋亡异常及炎症反应密切相关，最终可导致心功能下降甚至心力衰竭。目前MIRI的临床干预效果有限，机制尚未完全阐明，亟需探索新的治疗靶点。JAK2/STAT3信号通路在MIRI中具有重要心肌保护作用，可通过抑制氧化应激、凋亡与炎症发挥心脏保护效应。研究表明，龙血素能够调控该通路减轻心肌损伤，而龙血素A作为龙血竭的主要活性成分，其通过JAK2/STAT3通路干预MIRI 的具体机制仍有待系统阐明。本文就相关研究进行综述，旨在为心肌缺血再灌注损伤的防治提供理论依据，推动中医药在心血管疾病中的应用与发展。
[1] 刘明波, 何新叶, 杨晓红, 等.《中国心血管健康与疾病报告2024》要点解读[J].中国全科医学,2025,28(32):3989-4008..
[2]Algoet M, Janssens S, Himmelreich U, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation[J]. Trends in Cardiovascular Medicine,
2023,33(6):357-366.DOI:10.1016/j.tcm.2022.02.005.
[3]Mahdiani S, Omidkhoda N, Rezaee R, et al. Induction of JAK2/STAT3 pathway contributes to protective effects of different therapeutics against myocardial ischemia/reperfusion[J]. Biomed Pharmacother, 2022,155:113751.DOI:10.1016/j.biopha.2022.113751.
[4]Friedrich K, Dolznig H, Han X, et al. Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3[J]. Bioscience trends, 2017,11(1):1-8. DOI:10.5582/bst.2016.01250.
[5]Liao C L, Liu Y, Huang M Z, et al. Myocardial ischemia reperfusion injury is alleviated by curcumin-peptide hydrogel via upregulating autophagy and protecting mitochondrial function[J]. Stem Cell Res Ther, 2021,12(1):89.DOI:10.1186/s13287-020-02101-y.
[6]Liu C J, Yao L, Hu Y M, et al. Effect of Quercetin-Loaded Mesoporous Silica Nanoparticles on Myocardial Ischemia-Reperfusion Injury in Rats and Its Mechanism[J]. Int J Nanomedicine, 2021,16:741-752.DOI:10.2147/IJN.S277377.
[7]Li C, Zhang Y, Wang Q, et al. Dragon’s Blood exerts cardio-protection against myocardial injury through PI3K-AKT-mTOR signaling pathway in acute myocardial infarction mice model[J]. Journal of ethnopharmacology, 2018,227:279-289.DOI:10.1016/j.jep.2018.09.010.
[8]Musso T, Johnston J A, Linnekin D, et al. Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7[J]. The Journal of experimental medicine, 1995,181(4):1425-1431.DOI:10.1084/jem.181.4.1425.
[9]Zhao X, Qin Y, Niu Y, et al. RETRACTED: Matrine inhibits hypoxia/reoxygenation-induced apoptosis of cardiac microvascular endothelial cells in rats via the JAK2/STAT3 signaling pathway[J]. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018,106:117-124.DOI:10.1016/j.biopha.2018.06.003.
[10]Hu Z, Zhang S, Chen Y, et al. DTNA promotes HBV-induced hepatocellular carcinoma progression by activating STAT3 and regulating TGFβ1 and P53 signaling[J]. Life sciences, 2020,258:118029.DOI:10.1016/j.lfs.2020.118029.
[11]Guo B, Yu Y, Wang M, et al. Targeting the JAK2/STAT3 signaling pathway with natural plants and phytochemical ingredients: A novel therapeutic method for combatting cardiovascular diseases[J]. Biomed Pharmacother, 2024,172:116313.DOI:10.1016/j.biopha.2024.116313.
[12] 沈诚, 范士志, 陈建明. 抑制JAK/STAT通路对大鼠离体缺血再灌注心脏心功能的影响[J].医学临床研究,2006,(03):314-317.
[13] 魏成露, 冯庆敏, 陈宋程, 等. 心肌缺血再灌注损伤分子机制的研究进展[J].海南医学院学报,2022,28(16):1268-1274.DOI:10.13210/j.cnki.jhmu.20210507.002.
[14] 刘胜中, 甘崇志, 杨双强.JAK2/STAT3通过上调HSP70蛋白介导TTX心肌保护作用[J].西部医学,2011,23(03):415-418.
[15]Billah M, Ridiandries A, Allahwala U K, et al. Remote Ischemic Preconditioning induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway[J]. International journal of molecular sciences, 2020,21(5):1692.DOI:10.3390/ijms21051692.
[16]Chen P, Shang A, Yang J, et al. microRNA-874 inhibition targeting STAT3 protects the heart from ischemia-reperfusion injury by attenuating cardiomyocyte apoptosis in a mouse model[J]. Journal of cellular physiology, 2019,234(5):6182-6193.DOI:10.1002/jcp.27398.
[17]Zhao G, Yu L, Gao W, et al. Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress[J]. Acta pharmacologica Sinica, 2016,37(3):354-367.DOI:10.1038/aps.2015.136.
[18]Yang Q, Ji H, Modarresi Chahardehi A. JAK/STAT pathway in myocardial infarction: Crossroads of immune signaling and cardiac remodeling[J]. Molecular immunology, 2025,186:206-217.DOI:10.1016/j.molimm.2025.08.018.
[19] 杨潇, 张瑞芬. 中医药治疗心肌缺血再灌注损伤的实验研究进展[J].中医药学报,2019,47(1):120-123.DOI:10.19664/j.cnki.1002-2392.190032.
[20] 林忆龙, 文亦磊, 黄洪, 等. 龙血竭化学成分及药理作用研究进展[J].中国民族民间医药,2020,29(6):50-55.DOI:10.3969/j.issn.1007-8517.2020.6.zgmzmjyyzz202006014.
[21]刘芳, 戴荣继, 邓玉林, 等. 龙血竭总酚活血化瘀活性成分的虚拟筛选及初步活性研究[J]. 北京理工大学学报, 2015,35(2):218-220.DOI:10.15918/j.tbit1001-0645.2015.02.021.
[22]孟薇薇,王瑶瑶,戴荣继,等.龙血树叶化学成份及抗凝血作用初步研究[C]//中国化学会.中国化学会第26届学术年会有机化学分会场论文集.北京理工大学生命科学与技术学院; 北京理工亘元医药开发有限公司;,2008:118.
[23] 杨起江.Meta分析联合网络药理学及分子对接技术探讨龙血竭治疗心肌缺血再灌注损伤的疗效及作用机制[D]. 昆明理工大学,2022.DOI:10.27200/d.cnki.gkmlu.2022.000511.
[24] 杨天睿, 张海燕, 叶堃, 等. 龙血竭对体外心肌缺血再灌注树鼩模型细胞凋亡及内质网应激蛋白表达的影响[J].中华中医药杂志,2021,36(12):7037-7042.
[25] 陈品秋, 班玮康, 王文艳, 等. 龙血竭及其主要活性成分对脑缺血的药理作用与机制研究进展[J]. 中草药, 2023,54(18):6172-6184.DOI:10.7501/j.issn.0253-2670.2023.18.034.
[26]Meksuriyen D, Cordell G A. Retrodihydrochalcones from Dracaena loureiri[J]. J Nat Prod, 1988,51(6):1129-1135.DOI:10.1021/np50060a013.
[27]杨波, 郭建恩, 韩俊婷, 等. 龙血素A对大鼠局灶性脑缺血再灌注引起的脑损伤及机制探讨[J].中药新药与临床药理,2010,21(2):103-107.
[28] 黎丽清, 张钊, 陈乃宏. 龙血素A抑制中性粒细胞浸润改善光栓塞脑卒中模型小鼠脑血管损伤[J].世界科学技术-中医药现代化,2024,26(12):3246-3255.
[29]Hao H Z, He A D, Wang D C, et al. Antiplatelet activity of loureirin A by attenuating Akt phosphorylation:In vitro studies[J].Eur JPharmacol,2015,746:63-69. DOI:10.1016/j.ejphar.2014.10.059.
[30]Li C, Zhang Y, Wang Q, et al. Dragon’s Blood exerts cardio-protection against myocardial injury through PI3K-AKT-mTOR signaling pathway in acute myocardial infarction mice model[J]. J Ethnopharmacol, 2018,227:279-289.DOI:10.1016/j.jep.2018.09.010.
[31] 桑玉欣. 龙血素A抗大鼠血栓的作用及机制研究[D]. 大连医科大学,2015.
[32] 王笑宇. 龙血素A抗心肌细胞氧化应激损伤的研究[D]. 大连医科大学,2015.